3-27379241-A-T

Variant names:

• chr3-27379241-A-T
• rs371468517
• NM_001321103.2:c.3698+8T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321103.2(SLC4A7):​c.3698+8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,299,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SLC4A7 NM_001321103.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001842
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

Genes affected

SLC4A7 (HGNC:11033): (solute carrier family 4 member 7) This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

SLC4A7 Gene-Disease associations (from GenCC):

• cone-rod dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ENSG00000287348 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.3698+8T>A		splice_region_variant, intron_variant	Intron 25 of 25	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.3698+8T>A		splice_region_variant, intron_variant	Intron 25 of 25	1	NM_001321103.2	ENSP00000390394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1299770 Hom.: 0 Cov.: 20 AF XY: 0.00000155 AC XY: 1 AN XY: 645966

African (AFR) AF: 0.00 AC: 0 AN: 29836

American (AMR) AF: 0.00 AC: 0 AN: 35604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24674

East Asian (EAS) AF: 0.00 AC: 0 AN: 35310

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002198

Other (OTH) AF: 0.00 AC: 0 AN: 55160

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371468517; hg19: chr3-27420732;